This research examines defects in human erythropoiesis that lead to marked shortening of the red cell lifespan. In order to study these disoreders we have adopted the techniques of in vitro erythroid cell growth, examination of globin gene heterogeneity and the assembly of membrane protein. These studies together with an ongoing attempt to prove our capacity to develop prenatal diagnoses of the hemoglobinopathies are desinged to improve the status of patients with inherited disorders of the red cell. The work is performed both at the Children's Hospital Medical Center and in Dr. Harvey Lodish's laboratory at the Massachusetts Institute of Technology. Thus far, for the last year, we have been able to provide maps of human alpha and beta globin genes and have shown that the alpha thalassemia syndromes are not due to complete structural alpha gene deletions in all cases, aberrant genes are also noted. We have also detected a new form of beta thalassemia characterized by partial deletion of the beta gene. Utilizing this technique and ordinary fetoscopy we have been able to improve our technology for prenatal diagnosis of the hemoglobinopathies. The techniques are now being established worldwide. Our work on human erythropoiesis in vitro has shown that products of divising T-cells are necessary to influence the growth of erythroid precursors in plasma clot cultures. Work on the red cell membrane has focused on the physical state of spectrin and the timing of insertion of proteins into developing red cell membranes.